Mark DeWitt ’06 Leads Sickle Cell Gene Editing Team

Sickle-cell disease (SCD) is a group of blood disorders that includes sickle-cell anemia (SCA). The disease, which affects millions around the globe and can be fatal, is noteworthy in the history of biochemistry and genetics because in 1949 Caltech chemist (and Portland, Oregon native) Linus Pauling and co-workers determined that SCA was a “molecular disease,” it was due to a change in the molecular structure of a single hemoglobin molecule: disease-free individuals carry hemoglobin A, while those with SCA carried a different form called hemoglobin S. found in red blood cells. Work by other scientists eventually established that the disease followed a distinctive genetic pattern in that it was mainly inherited from one’s parents, and that the difference between hemoglobins A and S could be traced to a single nucleotide (“point mutation”) difference in DNA sequences.

Mark leads a study that has demonstrated that the CRISPR/Cas9 gene editing technology can “fix” the DNA in damaged human cells, and that the corrected cells will grow in mice. Mark tells the Times reporter, “What we have right now, if we can scale it up and make sure it works well, is already enough to form the basis of a clinical trial to cure sickle cell disease with gene editing.”